With triple quadrupole mass spectrometers (TQMS) and ion trap time-of-flight mass spectrometers (IT-TOFMS), an ion having a specific mass/charge ratio (m/z) is selected as a precursor ion from among various ions that are derived from the component being analyzed. The precursor ion is dissociated by collision induced dissociation (CID), and the product ions that are generated are subjected to mass spectroscopy to produce a MS/MS (=MS2) spectrum.
With a chromatograph-mass spectrometer that combines a mass spectrometer that is capable of performing liquid chromatography, gas chromatography and MS2 analysis, if the components that are present in a specimen are known, the MS2 spectrum of the target compound can be obtained by setting in advance as the analysis condition the mass/charge ratio of the precursor ion that is the subject of the MS2 analysis during the retention time of the component. However, if the components that are present in a specimen are unknown, it is not possible to set the mass/charge ratio of the precursor ion in advance, and it is not possible to obtain the results of the MS2 analysis of the unknown components that are present in the specimen in addition to the target component. Different from this, also known in the art are mass spectrometers that are equipped with a function (“automatic MS2” hereinafter) that automatically selects an appropriate precursor ion in real time and performs a MS2 analysis based on the results of an MS analysis that does not use CID.
For example, Patent Literature 1 describes performing a MS2 analysis by sequentially selecting a peak starting with the one with the highest signal strength among the plurality of peaks that appear in a MS spectrum generated by a MS analysis and performing MS2 analysis by automatically selecting as the precursor ion the ion species that correspond to the respective peaks. The same literature also describes performing MS2 analysis by selecting peaks whose signal strength fall within a predetermined strength range and automatically setting the corresponding ion species as the precursor ions. Furthermore, Patent Literature 2 and Non-Patent Literature 2 describe performing MS2 analysis that entails not just setting up a sequence based on signal strength or mass/charge ratio of the plurality of peaks that appear in a MS spectrum that is obtained from MS analyses but also using such factors as valence and mono-isotonic peaks to eliminate or preferentially select ions with specific mass and charge for the automatic selection of the precursor ions which are used for an MS2 analysis.
An overview of an automatic MS2 function in a usual chromatograph-mass spectrometer is described next with reference to FIG. 5. Here, one peak with the highest signal strength is selected as the only precursor ion from among the peaks having a signal strength higher than a threshold value th in the MS spectrum. However, an excluded ion list and a preferential ion list are separately provided, and ions with a mass/charge ratio that is registered in the excluded ions list are not selected as a precursor ion even if the afore-described criteria is met. Conversely, ions with a mass/charge ratio that is registered in the preferential ions list are selected as a precursor ion so long as there is a peak even if the afore-described criteria is not met. Ordinarily, the excluded ions list is used so that impurity components or interfering components that are known to be present in a specimen and components that are known in advance to not require an analysis are not selected as precursor ions. Conversely, the preferential ions list are used so that components that are of interest for analysis are selected as a precursor ion even if they may be present only in minute quantities. The number of precursor ions that can be selected for any one MS spectrum is limited since there is a constraint on the amount of time available for performing a MS2 analysis in real time.
Assume that a total ion current (total ion) chromatogram produces the waveform shown in FIG. 5(a) and that the MS spectrum identified as A is obtained at time t1. Based on the afore-described criteria regarding signal strength, peak f can be selected as a candidate as a precursor ion based on the MS spectrum. However, if the mass/charge ratio corresponding to peak f is registered in the excluded ions list, the ion corresponding to peak f is not selected as a precursor ion. On the other hand, even though the signal strength of peak g falls short of the threshold th, if the corresponding mass/charge ratio is registered in the preferential ions list, the ion corresponding to peak g is selected as a precursor ion, and an MS2 analysis on this precursor ion is started immediately (following the MS analysis). The MS2 spectrum that is obtained is identified as B.
Assume that the MS spectrum identified as C is obtained at a different time, time t2. This MS spectrum has five peaks whose signal strength exceeds the threshold th. Peaks are then selected in order starting with the peak with the highest strength. Assume that the mass/charge ratios corresponding to peaks b and d are registered on the excluded ions list. These peaks are then excluded, and the ion corresponding to the peak with the next highest strength, peak a, is selected as the precursor ion, and a MS2 analysis is immediately executed on the precursor ion. The result is the MS2 spectrum identified as D. With an analysis that uses the automatic MS2 function, an ordinary MS analysis which does not involve a CID is repeated, and if the results of the analyses show the presence of an ion that meets the precursor selection condition, the ion is used as a precursor ion, and the MS2 analysis is performed in real time.
The following problems occur with the analytic use of a chromatograph-mass spectrometer with an automatic MS2 function such as the afore-described. If the specimen being analyzed includes many components whose retention time is close to each other, the number of ions that are selected as precursor ion candidates becomes numerous near that retention time. If a MS2 analysis is performed while repeatedly selecting as the precursor ion only the ions that are derived from the same component, it is possible for important components to elute out of the column before ions that are derived from such important components are subjected to a MS2 analysis. In other words, a risk arises of failing to perform a MS2 analysis on the important components. To avoid this, it has been possible in the prior art to set as one condition for the selection of a precursor ion an upper limit to the number of times that ions with the identical mass/charge ratio (in actual practice, the mass/charge ratio that is deemed to be identical within the tolerated mass difference range) can be selected as a precursor ion.
However, with previous apparatuses, if a compound included an element such as bromine whose abundance ratio of stable isotopes is approximately 1:1, a possibility arises that after selecting ions that are derived from that compound as a precursor ion a predetermined number of times, ions that are derived from the same compound that include isotopes may continue to be selected as the precursor ion. The result would be for a MS2 analysis to not be performed on other compounds or, even if the MS2 analysis is performed, for the MS2 spectrum that is generated to not have sufficient sensitivity due to the drop in the concentration of that component.